Process for the preparation of abscisin ii



United States Patent O 3,504,021 PROCESS FOR THE PREPARATION OF ABSCISINII Donald L. Roberts, Robert A. Heckman, and Bonita P.

Hege, Winston-Salem, NC, assignors to R. J. Reynolds Tobacco Company,Winston-Salem, N.C., a corporation of New Jersey No Drawing. Filed Nov.2, 1966, Ser. No. 591,428 Int. Cl. C07c 51/00 US. Cl. 260-514 4 ClaimsABSTRACT OF THE DISCLOSURE Synthesis of the plant abscission honmone,abscisin II, by treating OL-lOl'lYlldBIlCflCOtBtC esters with a tertiaryalkyl chromate oxidizing agent followed by saponification.

This invention relates to a new method of synthesizing the plantabscission hormone, abscisin II.

As is known, the plant hormone abscisin II is anabscission-acceleratingsubstance which can be isolated from young cotton fruits and sycamoreleaves. Abscisin II chemically is 3-methyl-5-l-hydroxy-4-oxo-2,6,6-trimethyl- 2-cyclohexene 1 yl)-cis,trans-2,4-pentadienoic acid having the following structure:

CH CH CH CH J OH 0 CH3 COOH Synthetic production of this hormone isobviously desirable and the present invention provide a new syntheticmethod of producing this material.

The synthesis method of this invention involves treatingtat-ionylideneacetate esters with a tertiary alkyl chromate oxidizingagent followed by saponification to yield abscisin II. The synthesis canbe represented by the following reaction scheme:

CH CH (eis, trans isomer) The tit-ionylideneacetate esters which areemployed in the synthesis are the lower alkyl esters ofa-ionylideneacetic acid wherein R contains from 1 to 4 carbon atoms. Theratio of the cis,trans and trans,trans isomers of abscisin II dependsupon the ratio of the corresponding isomers in 3,504,021 Patented Mar.31, 1970 ice the it-ionylideneacetate esters which are employed in theoxidation; if pure cis,trans isomers of int-ionylideneacetate esters areused, abscisin II is obtained as the sole product.

The tertiary alkyl chromate oxidizing agents which are employed arethose containing from 4 to 6 carbon atoms in the alkyl group. Ifdesired, these oxidizing agents can be formed in situ in the reaction bythe use of chromium trioxide and a tertiary alkyl alcohol such as, forexample, t-butyl alcohol, t-amyl alcohol and2,3-dimethyl-2,3-butanediol. An excess of the tertiary alkyl chromateoxidizing agents is preferably employed, such as from 2 to 5 moles permole of the (at-ionylideneacetate ester. The oxidation of therx-ionylideneacetate esters is preferably carried out at an elevatedtemperature such as from about 60 to C. for a period suflicient toaccomplish oxidation, generally a period from about 1 to 24 hours.

The ionylideneacetate esters can be prepared from aionone according tomethods known in the art such as, for example, by the methods describedin I. Am. Chem. Soc., 77, 4111-4119 (1955) and also in Nippon KagakuZasshi, 79, 82331 (1958).

The following examples illustrate the synthesis method of the presentinvention.

EXAMPLE I (a) Preparation of methyl rat-ionylideneacetateTrimethylphosphonoacetate (50 g., 0.275 mole) was added dropwise to aslurry of 56% sodium hydride (13.2 g., 0.275 mole) in 500 milliliters of1,2-dimethoxyethane at 20. The mixture was stirred for one hour to allowfor gas evolution. a-Ionone (48 g., 0.25 mole) was added dropwise andthe mixture was heated under reflux for 3.5 hours. Water was then addedand the mixture was extracted with ether. The dried ether solution wasdistilled and a 66.5% yield of methyl a-ionylideneacetate was obtained.The ester was identified by its infrared spectra.

(b) Oxidation of methyl tat-ionylideneacetate A solution of chromiumtrioxide (26.8 g., 0.268 mole) in 100 milliliters of t-butyl alcoholcontaining 25 milliliters of acetic anhydride was added to methyla-ionylideneacetate (16.6 g., 0.063 mole) in 100 milliliters of tbutylalcohol at 100. The solution was refluxed for five hours, the residuewas diluted with water, oxalic acid was added, and the solutionextracted with ether. A total of 15 grams of crude product was obtained.The sample was chromato graphed, and the products were eluted fromsilicil acid with ether-pentane solutions. One gram of a mixture ofcis,trans and trans,trans of methyl 3-methyl- 5-(1-hydroxy-4-keto-2,6,6-trimethy1 2 cyclohexene-lyl)-2,4-pentadienoate was isolated.saponification of this fraction with 10% sodium hydroxide in methanolyielded abscisin II and its trans,trans-isomer.

EXAMPLE II t-Butyl chromate, prepared from 50 grams of chromium trioxidein 200 milliliters of tertiary butyl alcohol, was added with stirring to26.2 grams (0.1 mole) methyl ocionylideneacetate in milliliters oft-butyl alcohol at 100. The solution was heated under reflux for sevenhours. The reaction mixture was then diluted with water and oxalic acidwas added. The solution was extracted with ether; the ether solution waswashed with sodium carbonate and dried over sodium sulfate. Sixteengrams of crude products were obtained.

The sample was chromatographed over silicic acid and yielded 4.0 gramsof starting material and 2.0 grams of methyl1-hydroxy-4-keto-a-ionylideneacetate. This ester was saponified with 10%sodium hydroxide in methanol to yield abscisin II and itstrans,trans-isomer.

3 EXAMPLE III Twenty-five grams of ethyl a-ionylideneacetate were addedto t-butyl chromate prepared from 50 grams of chromium trioxide, 125milliliters of tertiary butyl alcohol, and 25 milliliters of aceticanhydride. The solution was refluxed for 2 /2 hours and then worked upas described in the previous procedure; 20.5 grams of crude productswere obtained in this reaction. The sample was chromatographed onsilicic acid and approximately 1 gram of ethyl1-hydroxy-4-keto-a-ionylidene acetate was obtained. This ester wassaponified with sodium hydroxide in methanol to yield abscisin II andits trans-transisomer.

It will be appreciated by those skilled in the art that various agentscan be employed in the saponification step of the herein describedsynthesis. For example, agents such as sodium hydroxide, potassiumhydroxide, sodium ethoxide, potassium t-butoxide and the like can beemployed to saponify the esters.

The abscisin II isomers (Formula I and Formula II) can be separated byslow crystallization from ether or benzene; abscisin II is the leastsoluble and crystallizes from ether in high purity.

Those modifications and equivalents Which fall within the spirit of theinvention and the scope of the appended claims are to be considered partof the invention.

We claim:

1. A process which comprises treating a lower alkyl ester ofa-ionylideneacetic acid with a tertiary alkyl chromate oxidizing agentand saponifying the oxidized reaction product to yield3-methyl-5-(l-hydroxy 4 oxo- 2,6,6-trimethyl-2-cyclohexene 1yl)-cis,trans-2,4-pentadienoic acid.

2. The process of claim 1 wherein treatment of the lower alkyl ester ofa-ionylideneacetic acid with a tertiary alkyl chromate oxidizing agentis carried out at a temperature in the range of about to about 3. Theprocess of claim 1 wherein a methyl ester of uionylideneacetic acid isemployed.

4. The process of claim 1 wherein the ethyl ester of a-ionylideneaceticacid is employed.

References Cited Nature, vol. 206, May 15, 1965. Agr. Biol. Chem. vol.29 (10) October 1965.

JAMES A. PATTEN, Primary Examiner PAUL J. KILLOS, Assistant ExaminerU.S. Cl. X.R. 260468

